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Biomedical subjects

G Cooper

Publications and source records attributed to G Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1997

INKBLOT: a neurological diagnostic decision support system integrating causal and anatomical knowledge.

As an initial step in the diagnostic process, human neurologists often use anatomical localization to constrain the set of diagnostic hypotheses deserving further consideration. We describe an automated system, INKBLOT-1, which uses anatomical localization in much the same way as human neurologists. Given a set of manifestations, INKBLOT-1 generates a set of hypothetical localizations relative to a coordinate system of nested cubes and then uses these localization(s) to explain the manifestations. We trace the reasoning mechanism utilized by INKBLOT-1 for a particular set of symptoms and show how INKBLOT-1 is able to generate novel hypotheses that explain the observed manifestations. In doing this, INKBLOT-1 demonstrates capabilities not demonstrated by previously described systems.

Artificial Intelligence↗
PubMed1997

Exposure to hepatitis A virus among blood donors, injecting drug users and prison entrants in Victoria.

To assess prevalence of exposure to hepatitis A virus (HAV) among injecting drug users (IDUs) and prison entrants in Victoria, and to compare this with prevalence of HAV among a reference population of blood donors, sera stored from two previous studies and from randomly selected blood donors were tested for total antibody to HAV. The first study was a longitudinal study of field-recruited IDUs from 1990 to 1992 and the second was a study of all prison entrants in 1991-92 (both studies were carried out in Victoria); blood donors were from the Australian Red Cross Blood Bank Victoria in 1995. Forty-five per cent of 2175 prison entrants and 51% of 293 IDUs were seropositive for HAV, compared with 30% of 2995 blood donors. When standardized for age against the blood donors, HAV seropositivity in IDUs was 44% and in prison entrants 60%. The strongest association of HAV seropositivity among the IDUs on multivariate analysis was a history of imprisonment. There are high rates of exposure to HAV among prison entrants, whether with a history of IDU or not, and among IDUs who have a prison history. The role of sharing contaminated injecting equipment in transmission of HAV seems to be less important than institutionalization per se. With adequate resourcing, both populations are appropriate targets for HAV vaccination, especially in a context of continuing decline of transmission of HAV in the general community.

Adolescent↗
PubMed1997

Basic determinants of myocardial hypertrophy: a review of molecular mechanisms.

The essential cardiac response to a fixed increase in hemodynamic load is an increase in cardiac mass. If the load increase is neither too severe initially nor indefinitely progressive, cardiac stress is renormalized, and compensated hypertrophy ensues. But hypertrophic compensation is often abrogated by progressively abnormal contractile performance per unit mass of myocardium, even when function at the organ level is maintained by the mass increase itself. That is, even when hypertrophy is appropriate to the load imposed, and in a manner analogous to dystrophic growth of skeletal muscle, specific phenotypic changes occurring during this growth response render compensation imperfect such that congestive heart failure ensues. This fact, and the fact that the presence of deleterious phenotypic changes in hypertrophied myocardium is critically dependent on the type of hemodynamic load imposed, mandates that cardiac hypertrophy be understood on the most basic level as a growth process if early, definitive interventions to prevent congestive heart failure following pathological hemodynamic overloads are to be realized.

Animals↗
PubMed1997

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy.

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Animals↗
PubMed1996

Butyl Acrylate/Vinyl Acetate Copolymer Latex Synthesis Using Ultrasound As an Initiator

The polymerization of oil-in-water (o/w) emulsions of monomeric species has been performed at 30°C (±5°C) under ultrasonic irradiation, in the absence of any added chemical initiators. Emulsions of butyl acrylate and vinyl acetate as well as emulsified mixtures of the two monomers have been reacted in this way. In all cases, the radicals formed as a result of the ultrasonic cavitation were sufficient to cause polymerization. Stable blue-white or white dispersions of polymer latex particles were obtained. The kinetics of the copolymerization process were monitored. The data obtained here show that the polymerization rate depends strongly upon the monomer concentration dissolved in the aqueous phase and on its vapor pressure. The more volatile of the monomers examined, vinyl acetate, was seen to have a markedly lower polymerization rate at equivalent monomer concentrations when compared to the butyl acrylate. This was attributed to monomer evaporation into the cavities formed by the ultrasound, causing a dampening of the cavitation process and hence a lower radical density. Data of particle sizes and polymer molecular weights for the latex samples support this hypothesis.

Journal Article↗
PubMed1996

Nudicauline and elatine as potent norditerpenoid ligands at rat neuronal alpha-bungarotoxin binding sites: importance of the 2-(methylsuccinimido)benzoyl moiety for neuronal nicotinic acetylcholine receptor binding.

Methyllycaconitine (MLA, 1) is a novel, potent probe for mammalian and insect nicotinic acetylcholine receptors (nAChR) and displays remarkable selectivity toward neuronal [125I]-alpha-bungarotoxin (alpha BgTX) binding sites that correspond to alpha 7-type nAChR in mammalian brain. We have shown that, among a number of selected norditerpenoid alkaloids, elatine (2) and nudicauline (3) are equipotent with, or better than, MLA (1) in binding to brain [125I]-alpha BgTX binding sites, with IC50 values of 6.1, 1.7, and 7.6 nM, respectively. The 2-((S)-methylsuccinimido)benzoyl moiety of these ligands is crucial for high-affinity binding, whereas structural modifications to the norditerpenoid core of the ligand can be tolerated without loss of activity or selectivity. In addition to MLA (1), elatine (2), and nudicauline (3), we have examined lycoctonine (4), inuline (6), lappaconitine (7), N-desacetyllappaconitine (8), delsoline (10), delcorine (11), deltaline (12), condelphine (13), and karacoline (14). This study therefore extends the range of norditerpenoids, other than MLA, which can be used to probe this important class of nAChR. All 12 alkaloids were assessed for activity at [3H]nicotine binding sites which are considered to represent alpha 4 beta 2 nAChR. Furthermore, the 1H and 13C NMR spectroscopic data of MLA and elatine have been critically compared.

Aconitine↗
PubMed1996

Molecular genetic analysis of sperm competition in the damselfly Ischnura elegans (Vander Linden).

Sperm competition can be a powerful selective force in the evolution of mating systems. Several odonate species have attracted study to assess the extent and mechanism of last-male sperm precedence. Members of the genus Ischnura (Zygoptera) display a particularly interesting range of mating systems, and Ischnura elegans was selected for study. Polymorphic microsatellites were cloned, sequenced and used to determine paternity of I. elegans larvae, to reveal patterns of sperm precedence. More than 3000 larvae, collected from both wild and captively bred I. elegans females, were typed for one or two microsatellite loci and paternity was determined by comparison with parental genotypes. Microsatellite typing showed that most wild-caught females had mated with several males. Analysis of offspring from females which mated in captivity showed that multiple-matings result in a large proportion of last-male sperm precedence (mean value for immediate last male precedence is 0.79 +/- 0.2 (+/- s.d.; n = 11, range = 0.44-1)). There is appreciable variation in the extent and patterns of immediate and longer-term precedence, which could reflect differences in male sperm removal ability or selective use of sperm by females.

Animals↗
PubMed1996

Translational initiation factor eIF-4E. A link between cardiac load and protein synthesis.

To define the coupling mechanism between cardiac load and the rate of protein synthesis, changes in the extent of eIF-4E phosphorylation were measured after imposition of a load. Electrically stimulated contraction of adult feline cardiocytes increased eIF-4E phosphorylation to 34% after 4 h, as compared with 8% phosphorylation in quiescent controls. However, eIF-4E phosphorylation did not increase upon electrical stimulation in the presence of 7.5 mM 2,3-butanedione monoxime, an inhibitor of actin-myosin cross-bridge cycling and active tension development. Treatment of adult cardiocytes with either 0.1 microM insulin or 0.1 microM phorbol 12-myristate 13-acetate increased eIF-4E phosphorylation to 23 and 64%, respectively, but these increases were not blocked by 2,3-butanedione monoxime. In canine models of acute hemodynamic overload in vivo, eIF-4E phosphorylation increased to 23% in response to left ventricular pressure overload as compared with 7% phosphorylation in controls. Acute volume overload had no effect on eIF-4E phosphorylation. These changes in eIF-4E phosphorylation account for differences in anabolic responses to acute pressure versus acute volume overload. These data suggest that eIF-4E phosphorylation is a mechanism by which increased cardiac load is coupled to accelerated rates of protein synthesis.

Animals↗
PubMed1996

Basis for increased microtubules in pressure-hypertrophied cardiocytes.

BACKGROUND: We have shown the levels of the sarcomere and the cardiocyte that a persistent increase in microtubule density accounts to a remarkable degree for the contractile dysfunction seen in pressure-overload right ventricular hypertrophy. In the present study, we have asked whether these linked phenotypic and contractile abnormalities are an immediate and direct effect of load input into the cardiocyte or instead a concomitant of hypertrophic growth in response to pressure overloading. METHODS AND RESULTS: The feline right ventricle was pressure-overloaded by pulmonary artery banding. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. The biogenesis of microtubules was estimated from Northern and Western blot analyses of tubulin mRNAs and proteins. These measurements were made in control cats and in operated cats during and after the completion of right ventricular hypertrophy; the left ventricle from each heart served as a normally loaded same-animal control. We have shown that the alterations in microtubule density and sarcomere mechanics are not an immediate consequence of pressure overloading but instead appear in parallel with the load-induced increase in cardiac mass. Of potential mechanistic importance, both these changes and increases in tubulin poly A+ mRNA and protein coexist indefinitely after a new, higher steady state of right ventricular mass is reached. CONCLUSIONS: Because we find persistent increases both in microtubules and in their biosynthetic precursors in pressure-hypertrophied myocardium, the mechanisms for this cytoskeletal abnormality must be sought through studies of the control both of microtubule stability and of tubulin synthesis.

Animals↗
PubMed1996

Incidence and outcome of overt gastrointestinal bleeding in patients undergoing bone marrow transplantation.

The purpose of this study was to determine the prevalence, clinical patterns, and outcomes of gastrointestinal bleeding in consecutive patients treated at one bone marrow transplant center. We reviewed the clinical course of 579 consecutive bone marrow transplant recipients who underwent therapy from January 1986 through December 1993. These patients were evaluated for overt gastrointestinal bleeding, defined as hematemesis, melena, hematochezia, or a combination. Overt gastrointestinal bleeding was defined in 43 of 579 patients (7.4%), including 25 men and 18 women undergoing transplantation for hematologic disorders (N = 29) and solid tumors (N = 14). After high-dose cytotoxic chemotherapy, patients were given allogeneic (N = 10) or autologous (N = 33) hematopoietic progenitor cell support obtained from bone marrow, peripheral blood, or both. H2 blockers, sucralfate, or a combination were administered to all patients as prophylactic therapy. Bleeding manifestations included hematemesis(N = 24, melena (N = 8), hematochezia (N = 7), and combinations (N = 4). The median time from bone marrow infusion to the onset of overt gastrointestinal bleeding was 7.5 days (range: 0-45 days). Fourteen patients had evidence of orthostatic hypotension attributable to gastrointestinal bleeding. Esophagogastroduodenoscopy was performed in 26 patients; 18 had diffuse esophagitis and gastritis. Two patients with bleeding ulcers underwent successful electrocautery. Colonoscopy was performed in five patients and revealed a cecal ulcer in one subject, tumor recurrence in one patient, and colitis in another. No patients underwent surgical intervention. Only ine patient died as a result of gastrointestinal bleeding. Overt gastrointestinal bleeding is uncommon in patients undergoing bone marrow transplantation; most episodes are self-limited and do not contribute to overall mortality. Endoscopy is primarily diagnostic as most patients do not have lesions amenable to therapeutic procedures.

Adolescent↗
PubMed1996

A self-help approach for high-risk drinking: effect of an initial assessment.

A self-help book was offered to persons wanting to quit or cut down on their alcohol use. Study participants (99 men, 56 women) were recruited through advertisements, screened by telephone, and randomly assigned to 1 of 2 conditions. Book by mail or Assessment + Book (30-min telephone motivational interview plus book by mail). At 3-month follow-up, significantly more participants qualified as moderate drinkers in the Assessment + Book condition (65% vs. 43%), by this criterion: < or = 12 drinks/week and < or = 10% heavy drinking days (5 + drinks if male and 4 + drinks if female; 13.6 g of ethanol per drink). At 12 months there was no effect of condition, but significantly more women than men were rated as moderate drinkers (71% vs. 52%). Collateral informants corroborated the participants' reports of drinking.

Adult↗
PubMed1996

Network analysis of human Y microsatellite haplotypes.

To investigate the utility of Y chromosome microsatellites for studying human male-lineage evolution, we typed samples from three populations for five tetranucleotide repeats and an Alu insertion polymorphism. We found very high levels of haplotype diversity and evidence that most mutations involve the gain or loss of only one repeat unit, implying that any given microsatellite haplotype may have arisen independently on two or more Y-chromosome lineages. Together, these factors suggest that interpretation of small sample sizes (< 30) will be problematic. By typing a large sample of individuals (n = 174) from one population, East Anglia, we were able to construct a haplotype network. The network exhibits a well-connected core structure of commoner haplotypes. Computer simulations based on this network estimate the convergence time for African and Caucasian groups may be between 1.4 and 1.8 times as long as the convergence of the East Anglian population. Based on our comparison between large and small sample sizes, we suggest that large sample sizes are necessary in order to interpret Y-microsatellite haplotypes, and that a network analysis of the type we describe may prove informative in future studies.

Base Sequence↗